During the past several years, studies of the neuroendocrine control of growth hormone and prolactin have suggested that the secretion of each of these hormones may involve both releasing and inhibiting factors of hypothalamic origin. As a consequence, simple measurement of plasma levels of the pituitary hormones cannot be considered adequate to detemine which of the neuroendocrine control mechanisms are responsible for the observed alterations in hormone secretion. The proposed studies will involve a multifaceted investigative effort related to (1) developing and refining specific and sensitive assays for each of the releasing and inhibiting factors controlling growth hormone and prolactin using both an in vivo rat bioassay system and an in vitro perifusion system using rat anterior pituitaries exposed to H3-and C14-amino acid coupled with immunoprecipitation of H3- or C14-labelled hormones; (2) a search for the presence of releasing and inhibiting factors in peripheral venous blood, portal hypophysial blood collected at the time of hypophysectomy, and cerebrospinal fluid of normal subjects and of patients with disorders of growth hormone and prolactin secretion via alterations in neurotransmitter functions will be used in an attempt to demonstrate changes in the levels of releasing and inhibiting factors; and (3) an investigation of the action of these relaeasing and inhibiting factors on the intracellular hormone synthesis, and on the molecular size heterogeneity of the released hormone. Studies will be performed on releasing and inhibiting factors extracted from hypothalamic tissue and from plasma in an attempt to demonstrate a similarity in their effects.